Cervical Cancer is the leading cause
of morbidity, mortality among women in
developing countries. As per GLOBOCON
2002(IARC) data, 500,000 women are
diagnosed & 270,000 deaths occur per year.
Projections indicate by 2050, more than 1
million new cases of cervical cancer will
be there each year. Although Prevention,
early detection and treatment are
established to be highly effective in
controlling cervical cancer, unfortunately
these are not optimaly utilized in
developing countries. So, the reality about
this cancer is though preventable but not
yet prevented. The objective of Cervical
cancer screening is to prevent the
occurrence of Invasive Cervical Cancer by
detecting in pre-invasive stages. Screening
tests like traditional Pap tests, Liquid based
Cytology, Visual Inspection with Acetic
Acid (VIA) and Lugols Iodine (VILI) and HPV
testing though have their own pros & cons
but if conducted in a proper way have
optimal accuracy in detecting CIN , early
asymptomatic preclinical invasive cancer.
Effective therapy like Cryotherapy , Laser
Ablation and Conisation, Loop
Electrosurgical Excision Procedure (LEEP),Cold knife Coagulation are widely
available to tackle these Precancerous
conditions . Pap test still remains to be
most practical, effective, fairly sensitive
and quite efficient to pin point the
suspicious group in which further
evaluation is required. Its role in mass
screening is unquestionable. Colposcopy
is a most useful aid to triage women with
positive tests, to assess the nature and
extent of precancerous lesions & guide to
take biopsy from exact side whenever
needed.The overall accuracy for detection
improves maximum if cytology and
colposcopy are simultaneously combined.It
is well told " Cytology discovers the crime
and Colposcopy locates the culprit".
"The first observation of Cancer cells in a
smear was the most thrilling experience
of my scientific career".
Dr George Nicholas Papanicolaou,1928
From the era of Papanicolaou who
was nominated for Nobel Prize to H Z
Hausen, who received nobel prize in the
yr 2008 for his work on HPV, there has
been a lot of innovations, changes and
modifications in the field of screening of
Cancer Cervix. It was Dr Papanicolaou who
first spread the concept of Cervical smear in 1928, considered as father of Modern
Cytology. In 1941, his research work
published in American J of Obstet. &
Gynecol titled "Diagnosis of Uterine Cancer
by Vaginal Smear" created a lot of
enthusiasm among various workers
worldwide in the field of screening.
Traditional Pap test has been
successful in reducing the incidence of
Cervical Cancer by 79% and mortality by
70% since 1950 but with a false negative
rate of 49% in detecting cancer precursor
lesions. Screening error can occur in 3
stages: Smear taking affecting smear
quality, Preparation of slides and
interpretation by cytologists. To alleviate
sampling and preparation errors newer
techniques have been developed to
provide more representative cell samples
of evenly dispersed cells in a thin layer
(monolayer) which aims to reduce material
such as blood ,pus and mucus from
obscuring cells during cytological
examination. The newer techniques are
based on high speed video microscopy
image interpretation software & field of
view computers to analyze and classify
images of Pap smear .Among these Liquid
based screening (LBS) including Thin Prep
(Cytyc Corporation) & Auto Cyte Prep
(tripath imaging which is a computerized
image processing device) have gained
much popularity in the developed world.
Liquid based Cytology transmits 80-90%
cells to the media, eliminates air drying. It
reduces the rate of unsatisfactory smears
of traditional pap test by 70% to 90%.LBS
has been used by 90% gynaecologists in
United States since 2003.
Over the last decade, remarkable
progress has been made in understanding
Cervical Carcinogenesis. An overwhelming
body of evidences show that infection with
various high risk Human Papilloma Virus
(HPV) is the central and necessary cause
for development of Cervical Cancers & its
precursor lesions. This fact was exploited
for development of molecular
technologies for viral detection to
overcome the limitations of Cytology as
screening procedure. HPV DNA testing
identifies women at risk for developing
cervical neoplasia without the inherent
subjectivity to cytology.HPV test can detect
HPV DNA in exfoliated cervical cells which
can detect about 100% Invasive Cancers,
75-90% precancerous lesions
(LSIL,CIN,HSIL) and 50% equivocal smear
(ASCUS).Various HPV testings are being
utilized as primary screening, triage of
equivocal pap smears or ASCUS and follow
up after treatment of CIN.
HPV Testing has a higher Sensitivity
and negative predictive value for
detection of pre-invasive disease than
cytology. But its important drawback is
lower specificity and low positive
predictive value for high grade lesions.
Outcome of HPV test as a primary screening
procedure (Various RCTs from Europe)
states that there is definite reduction in
incidence of high grade CIN ,3 to 5 yrs after
screening .LSIL and ASCUS represent the
largest fraction of abnormalities in cervical cancer screening. The ASCUS-LSIL Triage
study has investigated in a prospective
,randomized fashion for optimal
management of LSIL and ASCUS by
immediate Colposcopy ,HPV Triage and
repeat cytology concluded that HPV Triage
seemed to be at least as sensitive as
immediate colposcopy in detection of high
grade CIN ,where need for Colposcopy
referrals was halved. So HPV triage is the
best strategy for management of women
with ASCUS and this fact was incorporated
recently in international guidelines.HPV
Testing was also suggested to predict
residual or recurrent CIN in women treated
for high grade cervical lesions.
The two methods widely used for
HPV detection are PCR and Hybrid Capture
II (HC,Qiagen,Digene Corp).HC2 is a nuceic
acid hybridization assay for qualitative
detection of DNA of 13 oncogenic(Probe
A) and 5benign(Probe B) HPV types in
clinical specimen. It is the only HPV test
approved by Food & Drug Administration
(FDA ) for ASCUS triage and cervical cancer
screening in combination with Cytology
after the age of 30 yrs. Among PCR
techniques consensus PCR and type specific
PCR are commonly used. Roche Amplicor
HPV test is a commercial PCR based assay
for HPV detection which involves a pool of
13 HR -HPV as included in HC2 assay. The
most advanced HPV Genotyping
approaches are more appropriate for the
identification of individuals at risk of
disease than its presence or absence. After
consensus PCR amplifications, HPV types
can be discriminated by Reverse
Hybridization with type specific probes.
SPF PCR is a commercial INNO –LiPA HPV
assay which is capable of genotyping 25
different HPV types. Among the most
recent tests, HPV Viral Load, HPV
integration E2 status ,HPV RNA detection
(Pre Tect HPV Proofer) are promising for
screening of Cancer Cervix for the future.
Outcome from translational research also
identifies markers that reflect
dysregulation of cell cycle in cervical
neoplasia such as p 16, Ki -67 ,MCM
Proteins and Cyclin E which are expected
to be included in screening of Cancer cervix
in future.